DESCRIPTION: (Applicant's Abstract) Recent experiments indicate that Fischer 344, Long-Evans and Lewis rats vary in their sensitivity to the antinociceptive effects of low and intermediate efficacy mu opioids, as well as high efficacy mu opioids when tested in assays that employ relatively intense noxious stimuli. The proposed projects are designed to analyze further the fundamental differences in the responsiveness of various rat strains to the antinociceptive effects of opioid compounds. Two experimental manipulations, both aimed at challenging the mu opioid receptor system, will be evaluated in rats, using a warm-water (50, 52 and 56 degrees Celsius) tail-withdrawal procedure. Each of the proposed experiments will employ three rat strains and a series of mu opioids that vary (low, intermediate and high) in their intrinsic efficacy at the mu opioid receptor. In Experiment 1, the effects of mu opioids will be examined before and after the administration of the irreversible mu opioids antagonist beta-funaltrexamine (beta-FNA), whereas in Experiment 2 the ability of the opioid system to adapt to chronic exposure to morphine will be assessed. It is predicted that the rat strains most sensitive to the antinociceptive effects of mu opioids will be least sensitive to challenges with beta-FNA and chronic morphine. As such, the results of these experiments should provide critical information concerning the mu opioid receptor system and the resulting strain differences in responsiveness to mu opioids.